Inclusion Criteria:

* Age ≥ 18 years at the time of signing the informed consent form.
* Willing and able to adhere to the study visit schedule and other protocol requirements.
* Established diagnosis of low risk MDS (low risk per IPSS-R) or CMML 0-1 (CMML-0, for cases with \< 2% blasts in PB and \< 5% blasts in bone marrow (BM); CMML-1 for cases with \< 5% blasts in PB and BM; per 2016 WHO revision),14 with any one of the notable cytopenias as defined below:

1. Hgb \< 10 g/dL prior to enrollment
2. ANC \< 1.5×109/L
3. Platelets \< 100×109/L
* Participants may have received prior treatment with erythropoietin-stimulating agents (ESAs) such as darbepoetin, epoetin alfa, or similar agents. Prior exposure to luspatercept, imetelstat, or other newer agents is also permitted.
* TET2 mutation performed at a frequency of at least \> 2%.
* ECOG performance status of 0-2.
* Adequate organ function, defined as:

1. Serum total bilirubin \< 2x ULN, unless the subject has Gilbert's syndrome. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis. In these cases, approval from the study PI is required.
2. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate estimation.
3. Participants being enrolled on study on the basis of anemia, will only be eligible if folate, B12, serum iron, serum ferritin, total iron binding capacity, haptoglobin and peripheral smear within normal limits
4. Hepatitis panel negative for Hep B and Hep C infection
5. Negative for HIV infection
* Women of childbearing potential (WOCBP) may participate provided they have a negative serum pregnancy test at screening and a negative serum or urine pregnancy test within 72 h of starting treatment.
* WOCBP and males with partners who are WOCBP must agree to abstain from sexual intercourse or use effective contraception (methods that result in \< 1% pregnancy rates) during eltrombopag therapy and for at least 7 days after the last eltrombopag dose. Males with partners who are WOCBP must agree to use a barrier method.

Exclusion Criteria:

* High- and Very High-risk MDS (per IPSS-R)
* CMML-2
* Prior HMA exposure
* Platelet count \> 200×109/uL or leukocytosis of at least 25×10⁹/L
* Marrow fibrosis (MF 2-3)
* Results of bone marrow biopsy within 1 month of study entry (screening bone marrow biopsy) indicating high-risk MDS or CMML-2.
* Elevated LFTs (aminotransferases and bilirubin) \> 2x ULN
* Pre-existing cardiovascular disease (e.g., known coronary artery disease with percutaneous intervention or stroke within the last year) or arrhythmia (e.g., atrial fibrillation) associated with an increased risk of thromboembolic events, unless deemed acceptable by the enrolling treating physician.
* History of arterial or venous thromboembolism, and on anticoagulation.
* Severe hepatic impairment (Child-Pugh Class C)
* Recent history of cancer (i.e., within the past 5 years) with \> 50% chance of cancer recurrence in the next 5 years
* Current or prior history of hematologic malignancy
* Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
* Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.)
* Positive direct Coombs test
* Evidence of hypersplenism on physical exam
* Pregnant or lactating (women)